Mitapivat

点击蓝字 关注我们本周概览 本周EHA 2026年会（6月11-14日，斯德哥尔摩）发布多项重磅III期数据。实体瘤领域KRAS G12D抑制剂与HER2双抗齐头并进；代谢领域GLP-1双靶、APOC3 ASO及PK激活剂均验证硬终点获益；自免领域CAR-T疗法继续拓展治愈边界。一、 胰腺癌DN022150：KRAS G12D抑制剂II期，ORR 41.9% 药物/公司： DN022150 / 青峰医药（科睿药业子公司） 适应症： KRAS G12D突变晚期胰腺癌二线及以上 试验设计： I/II期，n=31（可评估） 指标结果 客观缓解率（ORR） 41.9% 疾病控制率（DCR） 93.5% ≥4级治疗相关不良事件 0例 胃肠道耐受性 良好 临床意义： KRAS G12D是胰腺癌最常见的驱动突变之一，目前尚无获批的靶向药物。DN022150在ORR和DCR两个疗效指标上均显示出有临床意义的抗肿瘤活性，且安全性特征优于传统化疗（无≥4级TRAE）。这一数据为KRAS G12D突变胰腺癌的后线治疗提供了一种潜在的口服靶向选择，III期注册研究的启动将进一步验证其疗效和安全性。 III期注册研究已启动，计划入组360例，主要终点PFS+OS。目前全球42款GRC12D靶向药在研，6款进III期，尚无任何一款获批。二、 乳腺癌KN026（KC-WISE）：HER2双抗联合化疗，胃癌二线PFS提升至7.1个月 药物/公司： Anlotinib（康尼妥单抗，KN026）/ 康宁杰瑞-石药集团 适应症： HER2阳性晚期胃癌或胃食管结合部腺癌，二线及以上（既往至少接受过一种含曲妥珠单抗方案后进展） 试验设计： 关键II/III期KC-WISE研究 指标KN026+化疗对照（化疗）结果 中位无进展生存期（mPFS）7.1个月 参照组HR=0.25 疾病进展风险降低75% 中位总生存期（mOS）19.6个月 参照组HR=0.29 约为化疗2倍 客观缓解率（ORR）55.8% 参照组的约5倍 — 不良反应 血液学毒性为主，临床可管 — 心脏毒性、腹泻、输注反应率低 临床意义： 胃癌HER2阳性患者在曲妥珠单抗耐药后，既往缺乏有效的HER2靶向药物。KN026联合化疗在PFS和OS上均显示出显著获益，mOS接近20个月、ORR超过55%，相较于对照组数据优势明显，且心脏和消化道毒性可控，为曲妥珠单抗经治后的HER2阳性胃癌患者提供了一种新的治疗选择。KN026-003：HER2双抗III期优效，挑战THP一线标准 药物/公司： KN026 + HB1801（白蛋白结合型多西他赛）/ 康宁杰瑞-石药集团 适应症： HER2阳性晚期乳腺癌一线治疗 试验设计： III期KN026-003（NCT05361902），n=880，1:1随机，中位随访约14个月试验组： KN026（HER2双抗）+ HB1801对照组： 曲妥珠单抗 + 帕妥珠单抗 + 多西他赛（THP，当前标准一线方案） 指标结果 主要终点PFS显著优于THP ，差异具有临床和统计学意义 总生存期（OS） 存在获益趋势，数据尚不成熟 安全性 良好，未见新安全性信号 临床意义： THP（曲妥珠单抗+帕妥珠单抗+多西他赛）是目前HER2阳性晚期乳腺癌的一线标准治疗。KN026-003作为全球首个在HER2阳性乳腺癌中头对头击败THP方案的III期研究，标志着HER2双抗类药物已在疗效上具备挑战现有标准治疗的潜力，其详细数据即将在学术会议公布，后续OS随访结果值得关注。三、 多发性骨髓瘤MonumenTAL-3（LBA）：GPRC5D双抗+达雷妥尤单抗，两组合均击败标准三药 药物/公司： Talquetamab（泰格贝妥）+ Daratumumab（达雷妥尤单抗）/ 杨森 适应症： 复发或难治性多发性骨髓瘤（RRMM），既往至少接受过来那度胺和一种蛋白酶体抑制剂后复发 试验设计： III期MonumenTAL-3，n=864，中位随访24.6个月，三组平行Tal-DP组： Talquetamab + 达雷妥尤单抗 + 泊马度胺 + 地塞米松Tal-D组： Talquetamab + 达雷妥尤单抗 + 地塞米松DPd对照组： 达雷妥尤单抗 + 泊马度胺 + 地塞米松（当前标准治疗） 人群特征：85%来那度胺难治，93%末线难治，12%既往暴露过抗CD38单抗。 有效性数据（中位随访24.6个月）： 核心终点Tal-DP（三药）Tal-D（两药）DPd（标准） 疾病进展或死亡风险降低72% （HR=0.28）67% （HR=0.33） 参照 24个月PFS率81.3% 77.6% 51.2% 死亡风险降低53% （HR=0.47）49% （HR=0.51） 参照 24个月OS率89.2% 87.9% 79.1% 疗效指标Tal-DPTal-DDPd 总缓解率（ORR） 88.2% 88.5% 77.6% 完全缓解率（≥CR） 71.1% 68.9% 34.5% MRD阴性率（≥CR人群） 52.3% 46.3% 15.9% 24个月维持缓解率 86.0% 79.8% 59.6% 仅接受过一线就来那度胺难治的亚组：Tal-DP风险降低81%，Tal-D降低77%。 安全性数据： 安全性指标Tal-DPTal-DDPd ≥3级治疗相关不良事件 94.9%74.8% 91.5% ≥3级中性粒细胞减少 较高（泊马度胺相关）29.2%（三组最低） 42.2% 严重感染（≥3级） 37.7%29.2%（三组最低） 42.2% CRS（任何级别） >50%（多为1-2级） — — ≥3级CRS<1% — — ≥3级神经毒性 <3% <3% — 临床意义： GPRC5D是近年来多发性骨髓瘤领域最受关注的创新靶点之一，Talquetamab作为全球首款GPRC5D双抗，其III期数据验证了该靶点的临床价值。Tal-D两药方案在PFS和OS上均显著优于标准DPd三药方案，且去除了泊马度胺的组合在≥3级中性粒细胞减少和感染发生率上更低，提示两药组合在疗效-安全性平衡上具有优势，对后续RRMM治疗格局将产生重要影响。四、 弥漫大B细胞淋巴瘤frontMIND（LBA）：Tafasitamab + R-CHOP一线，3年PFS率67.3% 药物/公司： Tafasitamab（Monjuvi/Minjuvi）+ 来那度胺 + R-CHOP / Incyte 适应症： 高危初治DLBCL或高级别B细胞淋巴瘤（HGBL），IPI评分3-5分（年轻患者aaIPI 2-3分） 试验设计： III期frontMIND（NCT04697780），中位随访35.2-35.9个月试验组： Tafa-Len-R-CHOP（tafasitamab + 来那度胺 + 标准R-CHOP）对照组： R-CHOP（标准方案） 有效性数据（中位随访35.2-35.9个月）： 核心终点Tafa-Len-R-CHOPR-CHOP结果 疾病进展或死亡风险降低25% — HR=0.75，p=0.0194 中位PFS 未达到 — — 2年PFS率 71.1% 62.9% +8.2% 3年PFS率67.3% 60.7% +6.6% 无事件生存期（EFS） — — HR=0.79，p=0.026 MRD阴性率81.3% 66.7% 差异显著 3年OS（期中分析） — — HR=0.85，p=0.2703（未达统计学阈值） 安全性数据： 指标Tafa-Len-R-CHOPR-CHOP 任何级别治疗相关不良事件 98.6% 97.1% ≥3级治疗相关不良事件 86.7% 76.1% 最常见≥3级事件 中性粒细胞减少（22.8%）、血小板减少（13.1%）、贫血 — 临床意义： 高危DLBCL（IPI 3-5分）患者即使接受R-CHOP标准治疗，仍有相当比例会出现疾病进展。frontMIND三年随访数据显示，tafasitamab联合来那度胺强化R-CHOP方案在PFS和EFS上达到统计学意义改善，且在ABC型和GCB型两个主要分子亚型中获益一致。尽管3年OS未达统计学显著性（中位随访35个月OS数据尚不成熟），但PFS和EFS的稳健获益对高危患者具有临床意义。五、 镰状细胞病Mitapivat（RISE UP III期）：血红蛋白应答40.6%，输血需求相对降低55.9% 药物/公司： Mitapivat（PK激活剂）/ Agios Pharmaceuticals 适应症： 镰状细胞病（16岁及以上） 试验设计： III期RISE UP，52周双盲期，mitapivat vs 安慰剂 主要终点——血红蛋白应答（第52周）： 指标Mitapivat安慰剂统计学显著性 血红蛋白应答率40.6% 2.9% p<0.0001 应答者平均血红蛋白增幅 +1.6 g/dL — — 应答定义：第24-52周平均血红蛋白较基线升高≥1.0 g/dL 输血负担改善： 指标Mitapivat安慰剂相对降幅 需要输血的受试者比例 23.9% 40.6%41.1% 平均红细胞输注单位/例 0.70 1.5955.9% 以上获益在是否合并使用羟基脲的患者中均观察到。 血红蛋白应答者post-hoc分析： 指标应答者非应答者降幅 年化镰状细胞疼痛危象（SCPC）发生率 2.20 2.9826% SCPC相关住院率 1.16 1.7634% SCPC急诊就诊率 1.11 2.3353% SCPC住院天数/年 7.83 12.3437% PROMIS疲劳评分改善 -5.19 -2.55 超出4.1分临床意义阈值 临床意义： 镰状细胞病的核心病理生理是血红蛋白聚合导致的镰状化和血管阻塞性危象（VOC）。Mitapivat作为首创的PK激活剂，通过提升红细胞内ATP水平改善红细胞代谢和脱水，减少血红蛋白聚合。RISE UP 52周详细数据证实了其不仅在血红蛋白提升上具有统计学显著性，更重要的是应答者的VOC相关住院、急诊就诊和住院天数均大幅降低，直接减轻了患者的急性医疗负担，疲劳改善也具有临床意义。六、 代谢性疾病玛仕度肽（III期GLORY-2）：60周减重18.55%，近半数患者减重≥20% 药物/公司： Mazdutide（玛仕度肽，GLP-1/GLP-2双靶）/ 信达生物 适应症： 中重度肥胖 试验设计： III期GLORY-2，n=462，2:1随机，60周双盲治疗 全人群（第60周）： 指标玛仕度肽9 mg安慰剂统计学显著性 平均体重降幅18.55% 3.02% P<0.001 减重≥20%的受试者比例44.0% 2.6% P<0.001 不合并2型糖尿病亚组（n=390）： 指标玛仕度肽9 mg安慰剂 平均体重降幅20.08% 2.81% 减重≥20%的受试者比例48.7% 3.1% 肝脏脂肪含量降幅（基线≥10%亚组）71.9% 升高5.1% 临床意义： 减重≥20%是判断代谢手术（如胃旁路术）指征的重要阈值，目前多数GLP-1类药物在这一指标上表现有限。玛仕度肽作为GLP-1/GLP-2双靶点药物，9 mg剂量在60周实现近半数患者减重达到这一水平，同时带来肝脏脂肪含量71.9%的显著降低，对合并代谢相关脂肪肝性肝病的肥胖患者具有额外代谢获益价值。CagriSema III期：HbA1c 8.8%→6.5%，体重减轻12% 药物/公司： CagriSema（cagrilintide 2.4 mg + semaglutide 2.4 mg）/ 诺和诺德 适应症： 2型糖尿病 REIMAGINE 3（基础胰岛素控制不佳，n约600，68周）： 在原有胰岛素治疗基础上添加CagriSema后，HbA1c从均值8.8%降至6.5%，体重减轻12%，无严重低血糖风险增加，无需增加胰岛素剂量。 REIMAGINE 2（二甲双胍控制不佳，n约900，68周）： 降糖和减重均显著优于单用司美格鲁肽对照组。 临床意义： 在基础胰岛素控制不佳的患者中，常规做法是增加胰岛素剂量，但这往往带来体重增加和低血糖风险。CagriSema在68周治疗期间实现HbA1c 2.3个百分点的降幅和12%的体重减轻，同时无需增加胰岛素剂量，提示GLP-1与胰淀素联合用药在血糖和体重双重管理上具有协同价值，有助于改善胰岛素使用患者的代谢困境。Olezarsen III期：甘油三酯降低64.8%，急性胰腺炎风险降低81% 药物/公司： Olezarsen（ASO）/ Ionis Pharmaceuticals 适应症： 严重高甘油三酯血症（合并糖尿病） 试验设计： 两项III期随机对照（n约1200），治疗12个月 指标Olezarsen 50 mgOlezarsen 80 mg安慰剂 甘油三酯水平降幅 57.4%64.8% — 急性胰腺炎年发生率1.55/100例 — 8.46/100例 急性胰腺炎风险降低81% — — 临床意义： 严重高甘油三酯血症（TG>500 mg/dL）患者面临急性胰腺炎这一危及生命的并发症风险。Olezarsen作为靶向APOC3的反义寡核苷酸（ASO），通过沉默APOC3基因表达降低甘油三酯水平，80 mg剂量12个月治疗使TG降低近65%，更重要的是急性胰腺炎发生率降低了81%，将年发生率从8.46%降至1.55%，对高危患者具有直接的临床保护价值。七、 皮肤疾病GX-03：特应性皮炎II期，4周EASI-75应答率70.4% 药物/公司： GX-03 / Turn Therapeutics（NASDAQ: TTRX） 适应症： 中重度特应性皮炎 试验设计： II期随机对照，n=50（中期分析） 时间节点GX-03安慰剂 第4周EASI-50应答率92.6% 65.2% 第4周EASI-75应答率70.4% — 第8周EASI-90应答率 51.9% 34.8% 因不良事件停药0例 — 临床意义： 特应性皮炎现有生物制剂和JAK抑制剂虽疗效显著，但存在感染风险增加、价格昂贵或需要注射给药等局限。GX-03在II期中期分析中4周即达到70.4%的EASI-75应答率，且无因不良事件停药，提示该药可能具有快速起效和良好安全性的特点，但样本量较小（n=50），需更大规模III期研究进一步验证。八、 风湿免疫CD19 CAR-T（COMPARE研究）：类风湿关节炎5/6无药缓解，ACPA降低>90% 研究： COMPARE研究 / EULAR 2026 Congress 适应症： 抗CCP阳性难治性类风湿关节炎 试验设计： CD19 CAR-T（mivocabtagene autoleucel），n=6 指标结果 DAS28-CRP改善幅度 中位49% ACR50应答率 4/6（67%） 无免疫抑制下持续缓解5/6（83%） 自身抗体（ACPA）中位降幅>90% B细胞重建后复发 0例 临床意义： 类风湿关节炎传统合成DMARDs和生物制剂治疗失败后，CAR-T细胞治疗提供了一种完全不依赖于长期免疫抑制的潜在治愈性路径。COMPARE研究中5/6患者在无任何免疫抑制治疗的情况下维持缓解，且B细胞重建后无一例复发，ACPA自身抗体水平降低超过90%，提示CAR-T清除B细胞后可能实现了致病性免疫记忆的深度重置。这一发现对理解自身免疫疾病的免疫病理和探索治疗新范式具有重要的科学意义。双靶CAR-T：系统性硬化症73%达到低疾病活动度 研究： CD19/BCMA双靶CAR-T / EULAR 2026 Congress 适应症： 难治性系统性硬化症 试验设计： n=11（合并间质性肺病8例） 指标结果 B细胞完全清除 11/11（100%） 皮肤厚度评分改善 显著 达到低疾病活动度73%（8/11） 基线合并ILD者（n=8）疾病稳定或改善80%（6/8） 临床意义： 系统性硬化症（硬皮病）是自身免疫病中治疗难度最大的疾病之一，皮肤和内脏纤维化进展以及合并间质性肺病（ILD）是主要死因。CD19/BCMA双靶CAR-T在11例难治性患者中实现73%达到低疾病活动度，且基线合并ILD的8例患者中80%疾病稳定或改善，提示CAR-T可能通过同时清除B细胞和浆细胞来抑制自身抗体驱动的纤维化进程，为这一高度未被满足的疾病领域提供了新的治疗思路。 八、 本周小结 肿瘤领域：胰腺癌KRAS G12D抑制剂DN022150（II期，n=31）ORR达41.9%、DCR达93.5%，无≥4级TRAE。HER2双抗KN026在胃癌二线（mPFS 7.1个月，HR=0.25；mOS 19.6个月，HR=0.29）及乳腺癌一线（III期头对头显著优于THP标准方案）均获阳性结果。 血液领域：MM领域MonumenTAL-3中，Talquetamab联合达雷妥尤单抗（两药/三药）较标准DPd方案降低72%/67%进展风险，24个月PFS率达77.6%/81.3%（对照51.2%），两药方案安全性更优。DLBCL高危一线frontMIND中，Tafa+R-CHOP降低25%进展风险（p=0.0194），3年PFS绝对获益6.6%（67.3% vs 60.7%）。 代谢与罕见病：镰状细胞病Mitapivat实现40.6%血红蛋白应答（对照2.9%），输血需求降55.9%，疼痛危象住院与急诊分别降34%和53%。玛仕度肽9 mg 60周减重18.55%（非糖尿病亚组20.08%），近半数减重≥20%，肝脏脂肪降71.9%。Olezarsen使甘油三酯降64.8%，急性胰腺炎风险骤降81%（年发生率1.55 vs 8.46/100例）。 自免突破：CD19 CAR-T在难治性RA中5/6实现无药缓解，ACPA自身抗体降幅>90%；CD19/BCMA双靶CAR-T在系统性硬化症中73%达低疾病活动度，合并间质性肺病者80%稳定或改善，CAR-T正从肿瘤走向自身免疫病的深度免疫重置。 免责声明：本文整理仅基于已公开的会议报告与期刊摘要，仅供医学专业人士参考，不构成任何治疗建议。临床决策请参照最新指南及产品说明书。具体试验数据请以官方发表来源及公司公告为准。 往期回顾：临床试验进展周报（2026年6月6日-12日） 临床试验进展周报（2026年5月30日-6月5日 ASCO 2026专刊） 临床试验进展周报（2026年5月23日-29日） 临床试验进展周报（2026年5月16日-22日） 临床试验进展周报（2026年5月9日-15日 ）关于「临研随笔」 聚焦全球临床试验与医学写作技能分享。 欢迎关注公众号，获取专业资源与深度内容。

Mitapivat demonstrated statistically significant improvement in hemoglobin response compared with placebo, with rapid onset and durable effectsNew analyses showed patients in mitapivat arm had clinically meaningful reduction in transfusion burden compared with placeboPatients in mitapivat arm who achieved hemoglobin response had clinically meaningful benefits across measures of sickle cell pain crises, fatigue, and other patient-reported outcomesMitapivat was well-tolerated, with a safety profile consistent with previous trials of mitapivat in sickle cell diseaseCompany to host investor conference call and webcast today at 9:00 a.m. ET (3:00 p.m. CEST) CAMBRIDGE, Mass., June 13, 2026 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a commercial-stage biopharmaceutical company focused on delivering innovative medicines for patients with rare diseases, today presented detailed results from the 52-week double-blind period of the global RISE UP Phase 3 trial of mitapivat, an oral pyruvate kinase (PK) activator, in patients aged 16 years or older with sickle cell disease. These efficacy and safety results, which include new transfusion burden and hemoglobin responder analyses reinforcing the strong anti-hemolytic profile of mitapivat, were presented during the distinguished Plenary Abstracts Session at the 31st European Hematology Association (EHA) Congress (EHA 2026) in Stockholm, Sweden. In November 2025, topline results from RISE UP demonstrated a significant improvement in the trial’s primary endpoint of hemoglobin response with mitapivat compared with placebo. The trial also met two key secondary endpoints, showing rapid and durable improvements in hemoglobin concentration and indirect bilirubin, a marker of hemolysis (red blood cell destruction). Although mitapivat showed a reduction in the annualized rate of sickle cell pain crises (SCPCs) compared with placebo, this primary endpoint did not reach statistical significance, and there was no overall difference between mitapivat and placebo for the key secondary endpoint measuring patient-reported fatigue. However, patients in the mitapivat arm who achieved a hemoglobin response experienced clinically meaningful reductions in the annualized rate of SCPCs and related hospitalizations, as well as improvements in fatigue. New RISE UP analyses, not previously disclosed by the company, further highlight the potential for mitapivat to offer clinical benefits for patients with sickle cell disease, as evidenced by a clinically meaningful reduction in transfusion burden and, for hemoglobin responders in the mitapivat arm, improvements observed across additional measures of pain and physical function. “Patients living with sickle cell disease are in critical need of new treatments that can effectively manage the debilitating impact of their condition,” said Biree Andemariam, M.D., Professor of Medicine and American Red Cross Endowed Chair in Transfusion Medicine, University of Connecticut Health, and a RISE UP trial investigator. “The RISE UP Phase 3 data presented today showcase the strong anti-hemolytic profile of mitapivat, with rapid and durable improvements in both hemoglobin and indirect bilirubin as well as a meaningful reduction in transfusion burden. Importantly, this anti-hemolytic effect is translating to clear clinical benefits, including improvements for hemoglobin responders across measures of sickle cell pain crises, pain, sleep, and physical function compared with non-responders. Together, these data reinforce the potential for mitapivat to improve the relentless physical toll that comes with living with sickle cell disease.” New RISE UP Phase 3 Trial Results at EHA 2026Reduction in Transfusion BurdenNew analyses from RISE UP show that mitapivat was associated with a clinically meaningful reduction in transfusion burden compared with placebo. Patients in the mitapivat arm had a 41.1% relative reduction in the proportion of patients requiring blood transfusions compared with placebo (23.9% with mitapivat vs. 40.6% with placebo), as well as a 55.9% relative reduction in average red blood cell units transfused per patient compared with placebo (0.70 units with mitapivat vs. 1.59 with placebo). These benefits were observed regardless of whether patients were also taking hydroxyurea. A reduction in transfusion burden in sickle cell disease can reflect decreased dependence on supportive care. Hemoglobin Responders Post-Hoc AnalysisAs previously reported, 40.6% of patients in the mitapivat arm achieved the primary endpoint of hemoglobin response (≥1.0 g/dL increase from baseline in average hemoglobin from Week 24 through Week 52) compared with 2.9% in the placebo arm, a statistically significant improvement (2-sided p<0.0001). Among these hemoglobin responders, the mean change from baseline in average hemoglobin concentration from Week 24 through Week 52 was 1.6 g/dL. A post-hoc analysis showed patients in the mitapivat arm who achieved a hemoglobin response also experienced clinically meaningful reductions in pain crises and related hospitalizations, including a 26% reduction in the annualized rate of SCPCs (2.20 for responders vs. 2.98 for non-responders) and 34% fewer related hospitalizations (1.16 for responders vs. 1.76 for non-responders). These patients also had improvements in healthcare utilization, with a 53% reduction in the annualized rate of emergency room visits for SCPCs (1.11 for responders vs. 2.33 for non-responders) and a 37% decrease in the annualized rate of hospitalization days for SCPCs (7.83 for responders vs. 12.34 for non-responders). Hemoglobin responders in the mitapivat arm also reported greater improvements in patient-reported fatigue scores than non-responders (-5.19 for responders vs. -2.55 for non-responders), as measured by change from baseline in average Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue 13a Short Form scores from Week 24 through Week 52. The magnitude of this improvement in hemoglobin responders exceeded the predefined 4.1-point threshold required to be considered clinically meaningful. In the mitapivat arm, improvements across several additional patient-reported outcomes, including measures of pain, sleep, and physical function, were observed for hemoglobin responders compared with non-responders: PROMIS Pain Intensity 1a: The mean change from baseline was -1.63 points for hemoglobin responders and -0.59 for non-responders, with a least squares mean (LSM) difference of -1.04 (95% confidence interval [CI]: -1.66 to -0.42), favoring hemoglobin responders. The LSM difference is used throughout to represent the model-adjusted difference between hemoglobin responders and non-responders.Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact: The mean change from baseline was 4.09 points for hemoglobin responders and 0.85 for non-responders, with an LSM difference of 3.24 (95% CI: 1.18 to 5.30), favoring hemoglobin responders.PROMIS Physical Functioning 8a: The mean change from baseline was 5.30 points for hemoglobin responders and 1.79 for non-responders, with an LSM difference of 3.51 (95% CI: 0.62 to 6.39), favoring hemoglobin responders.ASCQ-Me Sleep Impact: The mean change from baseline was 2.39 points for hemoglobin responders and -0.48 for non-responders, with an LSM difference of 2.87 (95% CI: 0.22 to 5.53), favoring hemoglobin responders.EuroQol-5 Dimension Visual Analog Scale (EQ-5D VAS): The mean change from baseline was 3.27 points for hemoglobin responders and -6.77 for non-responders, with an LSM difference of 10.04 (95% CI: 2.41 to 17.66), favoring hemoglobin responders. “Having the opportunity to present these comprehensive results during the EHA 2026 Plenary Session highlights the strength of the RISE UP Phase 3 data – the first pivotal trial to validate pyruvate kinase activation as a new treatment approach in sickle cell disease,” said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. “Building on over a decade of clinical experience with mitapivat across several hemolytic anemias, these results reinforce both its consistent benefits and its well-established safety profile, which is supported by over 1,300 patient-years of data. Taken together, mitapivat represents a differentiated anti-hemolytic approach that can provide meaningful clinical benefits for patients with sickle cell disease – an underserved population in desperate need of innovative therapies.” Safety Profile Mitapivat was well-tolerated, with a safety profile consistent with previous trials of mitapivat in sickle cell disease. The percentage of patients with any reported treatment-emergent adverse events was similar between the mitapivat and placebo arms (97.1% vs. 98.6%, respectively). No treatment-related deaths occurred during the trial. EHA 2026 Investor Event Agios will host a conference call and live webcast during EHA 2026 today, June 13, 2026, at 9:00 a.m. ET (3:00 p.m. CEST). The live webcast will be accessible on the Investors section of the company’s website (www.agios.com) under the “Events & Presentations” tab. A replay of the webcast will be available on the company’s website approximately two hours after the event. About Sickle Cell DiseaseSickle cell disease is a rare, inherited blood disorder caused by the production of abnormal hemoglobin that disrupts the ability of red blood cells to carry oxygen throughout the body. As a result, red blood cells become rigid and sickle-shaped, causing deformation of red blood cell membranes and the premature death of the cells. These effects lead to chronic hemolytic anemia, vaso-occlusion, and a cascade of severe and life-threatening complications, including long-term damage to the lungs, kidneys, and cardiovascular system. Due to its physical toll, sickle cell disease imposes a profound burden on patients and their families, marked by increased healthcare needs and early mortality. About Mitapivat in Sickle Cell DiseaseMitapivat, an oral pyruvate kinase (PK) activator, is designed to enhance the process by which red blood cells produce energy. This approach has the potential to improve red blood cell health by increasing ATP levels to support increased energy demands and lowering levels of a molecule called 2,3-diphosphoglycerate (2,3-DPG). In sickle cell disease, increased stress on red blood cells results in elevated levels of 2,3-DPG, which raises the likelihood that red blood cells develop the abnormal “sickle” shape that triggers vaso-occlusive crises. In May 2026, Agios announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for the accelerated approval of mitapivat in sickle cell disease. About the RISE UP Phase 3 TrialThe global RISE UP Phase 3 trial (NCT05031780) is evaluating the efficacy and safety of mitapivat in patients with sickle cell disease aged 16 years or older, representative of the global population. The trial included a 52-week, double-blind, randomized, placebo-controlled period, in which 207 participants were randomized 2:1 to receive oral mitapivat (100 mg) twice daily (n=138) or matched-placebo (n=69). To comprehensively evaluate objective measures of hemolysis alongside other clinically relevant outcomes in sickle cell disease, the double-blind period of RISE UP included two primary endpoints – hemoglobin response and annualized rate of sickle cell pain crises – as well as five key secondary endpoints: Average change from baseline in hemoglobin concentration from Week 24 through Week 52Average change from baseline in indirect bilirubin from Week 24 through Week 52Average change from baseline in Patient Reported Outcome Measurement Information System Fatigue 13a (PROMIS Fatigue) Short Form scores from Week 24 through Week 52Annualized frequency of hospitalizations for sickle cell pain crisesAverage change from baseline in percent reticulocyte levels from Week 24 through Week 52 Of the 176 participants who completed the double-blind period of the trial, nearly all (n=174/176) opted to transition into a 216-week open-label extension (OLE) period, during which all participants receive mitapivat. About Agios: Fueled by Connections to Transform Rare Diseases™ At Agios, our vision is to redefine the future of rare disease treatment. Fueled by connections, we build trusted partnerships with communities – collaborating to develop and deliver innovative medicines that have the potential to transform lives. With a foundation in hematology, we combine biological expertise with real-world insights to advance a growing pipeline of rare disease medicines that reflect the priorities of the people we serve. Agios is a commercial-stage biopharmaceutical company headquartered in Cambridge, Massachusetts. To learn more, visit www.agios.com and follow us on LinkedIn and X. Available Information about Agios To achieve broad dissemination, Agios may disclose information to the public through a variety of disclosure channels including press releases, SEC filings, and public conference calls and webcasts. Some of the information distributed through these disclosure channels may be considered material information. Investors and others should note that Agios plans to use its website (www.agios.com) as a distribution channel to announce and give notice of Agios’ upcoming events and presentations (including, but not limited to, presentations at medical or healthcare conferences). Such information, which may be deemed material, will be available on the Investors section of the company’s website under the “Events & Presentations” tab. In addition, you may sign up to automatically receive email alerts about Agios’ upcoming events and presentations (“Calendar Alerts”) by visiting the “Email Alerts” option under the “IR Resources” tab of the Investors section of the company’s website and submitting your email address. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of mitapivat and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of pandemics or other public health emergencies to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to establish and maintain key collaborations; uncertainty regarding any royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236 or cevidoplenib, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios’ cash and cash equivalents; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.Contacts:Investor ContactMorgan Sanford, Vice President, Investor Relations Agios Pharmaceuticalsmorgan.sanford@agios.com Media ContactEamonn Nolan, Senior Director, Corporate CommunicationsAgios Pharmaceuticalseamonn.nolan@agios.com